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| </table> | | </table> |
| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/TNR9_HUMAN TNR9_HUMAN] Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation. | | [https://www.uniprot.org/uniprot/TNFL9_HUMAN TNFL9_HUMAN] Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages. |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand-blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate utomilumab is a milder agonist than urelumab. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.
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| Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.,Chin SM, Kimberlin CR, Roe-Zurz Z, Zhang P, Xu A, Liao-Chan S, Sen D, Nager AR, Oakdale NS, Brown C, Wang F, Yang Y, Lindquist K, Yeung YA, Salek-Ardakani S, Chaparro-Riggers J Nat Commun. 2018 Nov 8;9(1):4679. doi: 10.1038/s41467-018-07136-7. PMID:30410017<ref>PMID:30410017</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6mgp" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] | | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] |
| *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] | | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |